Navigating Rare Disorders

The arrival of a newborn is generally a time for much joy and festivities. Having a child with normal features and signs of alertness is a huge relief, naturally, for any mother. Genetic disorders, are, thankfully, rare.

There are however, instances, when signs of abnormal development like cri-du-chat (cat’s cry), slanted eye, cleft lip and palate, extra or missing toes and fingers are seen. Some symptoms like late development or problems with vision can emerge later in infancy as well.

Developmental disorders can be diagnosed in pregnancy. Tests are available for checking the levels of proteins like alpha-fetoprotein and hormones like beta-estriol in maternal blood in the 12th and 13th week of pregnancy. There are ultrasound tests to judge the thickness of the skin fold on a baby’s neck, known as nuchal translucency tests. Although, these tests have been in use for several years now, they have a gross predictive value. By and large, these tests can help a doctor understand whether the fetus has any genetic abnormalities or not. However, the error rate for biochemistry-based tests can be as high as 15%. Depending upon the risk of outcome of these preliminary tests, gynecologists can decide whether to conduct more invasive tests such as amniocentesis or chorionic villus sampling or not. The pain point here is that these invasive tests also pose a risk to the pregnancy.

With latest advances in science, it is now possible to isolate a baby’s DNA from the mother’s blood. This development has ushered in a new era of prenatal diagnostic tests- Non-Invasive Prenatal Testing (NIPT). NIPT is as simple as drawing a small sample of blood from the expectant mother and handing it over to a Strand representative. Once the baby’s DNA is isolated, there are sophisticated tests to check for chromosomal abnormalities like translocation (part or whole of a chromosome quite literally jumping out of its place and joining with other chromosomes) or triploidy (one extra chromosome added to the regular pair, making it a triple chromosome). So, not only are NIPT tests less invasive as compared to the older tests, they are also more accurate in pinpointing the exact nature of DNA damage.

An added bonus is that the error rate in DNA-based NIPT is rather low- false negatives are rare with this new technique and the sensitivity of the tests is 100%.

The saga of rare disorders is not limited to developmental deficits in infancy alone. There are rare disorders like muscular dystrophies that can become evident in adulthood. In such cases, the signs and symptoms can appear when an individual is well into their 20s or 30s.

Again, here is a situation where genetic tests like the Strand Clinical Exome test, can provide very definite answers. This test has been used to diagnose several rare disorders like LAMA2 muscular dystrophy, Kabuki syndrome, and Joubert syndrome, to name a few. While a clear-cut understanding of the cause of a rare disorder provides a sense of relief and closure to the patients and caregivers, there are also cases like ataxia caused by vitamin E deficiency (AVED), which, once accurately diagnosed, are reversible! Patients can experience relief from the symptoms that they experience.

Take the case of Vikram Reddy* who experienced muscle weakness and gradual loss of strength at the age of 27. He consulted several doctors in the USA as well as in India to understand what was causing this sudden dysfunction. Finally, he was advised genetic analysis by an expert doctor from south India. When his DNA was analysed at Strand, mutations in the GNE gene were identified. The icing on the cake was that, once diagnosed, this condition was treatable with sialic acid supplements.

Incidence of rare genetic disorders in a person can cause much heartache and confusion. However, one need not adopt a fatalistic attitude. There are solutions available.

*- Name changed to protect patient privacy